Colorectal cancer (CRC) is the third most common cancer in both men and women, and accounts for almost 10% of all cancer deaths. There are several recommended screening methods for CRC, including colonoscopy and FOBT. Colonoscopy is the current gold standard, yet it is invasive and expensive, and FOBT is not sufficiently sensitive. It is recognized that CRC is curable by resection when localized, however, only 44% of US adults over the age of 50 undergo screening. There is a need for the development of non invasive, more acceptable, yet accurate methods of screening. Our goal is to identify CRC specific serum biomarkers, and to develop and commercialize a serum-based immunodiagnostic assay for CRC detection or screening. We have developed proprietary technologies to identify, validate and develop biomarkers for the detection of major cancers. Our innovative antibody-based approach involves: i) a collection of antibodies raised against known and unknown human proteins; ii) a proprietary protein array referred to as Matrix Protein Array Technology (MPAT) allowing multiplex analysis of a large number of clinical samples using a large number of antibodies; and iii) a collection of tissue and sera specimens from major cancers and controls. In our CRC program, we have identified six CRC tissue specific biomarkers and generated monoclonal antibodies (mAb) that display CRC specificity in tissue samples, as based on MPAT and conventional immunohistochemistry data. In this SBIR Phase I project we propose to test whether the six CRC tissue specific biomarkers are found in patient serum. To this end, we will screen serum samples using the MPAT and the tissue specific mAb against the CRC tissue biomarkers. First we will use small sample sets in pilot experiments, then we will confirm the results in up to 150 CRC and non-CRC serum samples (including benign, inflammatory and normal controls). Statistical analysis of the data points generated in this study will enable us to identify a panel of serum-based biomarkers. Selected biomarkers will be further validated in Phase II, thus leading to the development of an immunodiagnostic assay for CRC detection. The innovative aspects of this proposal are the development of novel biomarkers and novel mAb with clinical applications in CRC detection, and the rapid translation of these products to the patient with the support of clinical collaborators, EDRN validation samples, biostatistics and business consultants. PUBLIC HEALTH RELEVANCE: Colorectal cancer (CRC) is the third most common cancer in both men and women, and the second most common cause of death by cancer in the industrialized world. There are several recommended screening methods for CRC, which are either invasive or not sufficiently sensitive, and only 44% of US adults over 50 undergo screening. A serum-based immunodiagnostic assay for CRC detection or screening would be safer, more cost-effective and user-friendly than currently available methods. [unreadable] [unreadable] [unreadable]